X-ray fluorescence, XRF, is a technique widely used in some technical areas. X-rays are directed at a sample and secondary X-rays are emitted from the sample. The secondary X-rays are dependent on the elements contained in the sample and the intensity of the emitted X-rays can be used to determine the concentration of the element in the sample.
The intensities of emitted X-ray fluorescence are dependent not only on the concentration of the relevant element but also on the preparation of the sample and the matrix within which the element is contained. Sample preparation is accordingly important.
For accurate measurement, X-ray fluorescence apparatus needs to be calibrated against a suitable reference sample which should be similar to the sample being measured. Quantitative measurements can then be obtained by comparing the X-rays emitted from the reference sample and the test sample.
Reference samples/materials for many applications of XRF are commercially available. However, in order to use XRF in a wider range of commercial applications, including for example the pharmaceutical sector, there is a need for suitable reference samples.
The use of XRF for pharmaceuticals has been discussed by Ian Campbell, et al, “The Use of EDXRF for Pharmaceutical Material Elemental Analysis”, American Pharmaceutical Review (2012), which is presently available electronically at: www.americanpharmaceuticalreview.com/1504-White-Papers-Application-Notes/124874-The-Use-of-EDXRF-for-Pharmaceutical-Material-Elemental-Analysis/-. This paper discusses the application of XRF in this sector.
The reference samples discussed in that paper are mentioned to be prepared using a cellulose excipient material as the matrix and using organometallics. In such a process, the starting point is a solution of the metal in the form of an organometallic dissolved in toluene.
However, preparing reliable standards in this way has proved to be difficult time consuming and potentially hazardous to health.
Further, suitable dry reference standards for pharmaceuticals are not available commercially.
The accurate measurement of elements, for example metallic elements in particular, may be required for a number of reasons. There may be a need to check that any elements that may have been involved in the manufacture of the pharmaceutical, for example as catalysts, are not present in the product. There may be a need to check that there is no contamination which could potentially occur in a number of ways. Such checks may be chosen by the manufacturer or required by national or international standards bodies responsible for health and/or safety.
Accordingly, there is a need for a way of preparing reference standards including a matrix of material typically used as a pharmaceutical excipient and for the standards produced by such a method.